Oxazines have brought much synthetic interest due to their extensive biological activities. These are the important category of heterocycles, which may be formally derived from benzene and its reduction products by convenient substitution of carbon (and hydrogen) atoms by nitrogen and oxygen. In the last few decades, oxazine derivatives have documented as worthy synthetic intermediates and also blessed with notable sedative, analgesic, anticonvulsant, antipyretic, antimicrobial, antitubercular, antimalarial, antioxidant, and anticancer activities. Nowadays, it is important to develop new classes of compounds with more effective mechanisms due to drug resistance activity in which the ability of drug to effectively treat disease can be reduced. The aim of the article is to collect and make a more generalized review on the synthesis of oxazine derivatives and their pharmaceutical and biological activities. We hope this review will provide ample references for the researchers concerned with azines in generally and oxazines in particular.

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Tetrahydrocurcumin (THC) is a major metabolite of curcumin and plays an important role in curcumin-induced biological effects. THC is a promising preventive and chemotherapeutic agent for cancer. A series of new pyrazole derivatives of THC have been synthesized as potent anticancer agents. Direct condensation of THC with various substituted hydrazines leads to new pyrazole derivatives of THC (1–18). The prepared compounds have been evaluated via in vitro MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay for their cell proliferation-inhibitory activity against human lung adenocarcinoma (A549), human cervical carcinoma (HeLa) and human breast carcinoma (MCF-7) cells. Most derivatives show significantly higher anticancer activity against all three tested cancer cell lines than the parent compound THC. Several compounds (7, 8, 12, 13 and 15) display promising anticancer activity against MCF-7 cell line with IC50 values ranging from 5.8 to 9.3 µM. The most active compound (8) is substituted with 4-bromophenyl group at the pyrazole ring and inhibits the growth of all three tested cancer cell lines with an IC50 values of (8.0 µM, A549), (9.8 µM, HeLa) and (5.8 µM, MCF-7). The obtained compounds can be a good starting point for the development of new lead molecules in the fight against cancer.Graphical Abstract

Dedictation (To Prof. Salem Mahal, in his memory) Tetrahydrocurcumin (THC) is a metabolite of curcumin and a valuable lead structure in medicinal chemistry due to its curcumin-induced biological effects and its derivatives can be promising antitumor agents. Thirteen Schiff base derivatives of THC (1-13) were synthesized by direct condensation of THC with various primary amines in moderate to very good yield (45-94%) and their structures confirmed by 1 H NMR, 13 C NMR, HR-ESI-MS and IR techniques. Furthermore, these compounds were screened for in vitro anticancer activity against three human cancer cell lines including human epithelial lung carcinoma (A549), human epithelial cervical cancer (HeLa) and human breast adenocarcinoma (MCF-7). Most compounds exhibit moderate to good anticancer activity against all three tested cell lines and are significantly more active than THC. Compound 12 bears an N-(4-trifluromethyl)phenylethyl group and is the most active compound with IC 50 values ranging from 4.8 to 12.7 μM. The results obtained herein are important for further structure modifications of THC and the exploitation of the therapeutic potential of THC derivatives as anticancer agents.